The goals of this project are to characterize the nature and mode of action of suppressor cells in the peripheral blood of normal humans and in humans with depressed cellular immunity. In particular, we are studying the prostaglandin producing suppressor cell, a glass adherent mononuclear cell that secretes prostaglandin E2 (PGE2) which in turn suppresses the T cell response to mitogens and antigens in vitro. We have demonstrated a high affinity binding site for PGE2 on human lymphocytes. We used the cyclic AMP response to PGE2 as an indicator for cell surface receptors. Using such an assay, we found that PGE2 receptors were located on T cells and B cells. However, among the T cell population, these receptors appear to be concentrated on the population of T cells bearing an Fc receptor for IgG (T gamma cells). T gamma cells only make up approximately 10% of the T cell population. Thus, while PGE2 would appear to inhibit all T cell proliferation, only T gamma cells would appear to have receptors for this compound. This would suggest that prostaglandin inhibit T cell proliferation by activating a T gamma subpopulation which in turn suppresses the remainng T cells. Our research goal for the coming year include determining whether all T cells bear receptors for PGE2 or only subfraction of these cells. We have recently determined that approximately 50% of T gamma cells bear surface Ia. Therefore, we will determine if both the Ia positive T gamma cells and the Ia negative T gamma cells respond to PGE2 with a rise in cyclic AMP.